Cognitive, behavioural and psychological barriers to the prevention of severe hypoglycaemia: A qualitative study of adults with type 1 diabetes

Objectives: Severe hypoglycaemia affects approximately one in three people with type 1 diabetes and is the most serious side effect of insulin therapy. Our aim was to explore individualistic drivers of severe hypoglycaemia events. Methods: In-depth semi-structured interviews were conducted with a purposive sample of 17 adults with type 1 diabetes and a history of recurrent severe hypoglycaemia, to elicit experiences of hypoglycaemia (symptoms/awareness, progression from mild to severe and strategies for prevention/treatment). Interviews were analysed using an adapted grounded theory approach. Results: Three main themes emerged: hypoglycaemia-induced cognitive impairment, behavioural factors and psychological factors. Despite experiencing early hypoglycaemic symptoms, individuals often delayed intervention due to impaired/distracted attention, inaccurate risk assessment, embarrassment, worry about rebound hyperglycaemia or unavailability of preferred glucose source. Delay coupled with use of a slow-acting glucose source compromised prevention of severe hypoglycaemia. Conclusion: Our qualitative data highlight the multifaceted, idiosyncratic nature of severe hypoglycaemia and confirm that individuals with a history of recurrent severe hypoglycaemia may have specific thought and behaviour risk profiles. Individualised prevention plans are required, emphasising both the need to attend actively to mild hypoglycaemic symptoms and to intervene promptly with an appropriate, patient-preferred glucose source to prevent progression to severe hypoglycaemia

Seismic data reveal eastern Black Sea Basin structure

Rifted continental margins are formed by progressive extension of the lithosphere. The development of these margins plays an integral role in the plate tectonic cycle, and an understanding of the extensional process underpins much hydrocarbon exploration.A key issue is whether the lithosphere extends uniformly, or whether extension varies with depth. Crustal extension may be determined using seismic techniques. Lithospheric extension may be inferred from the waterloaded subsidence history, determined from the pattern of sedimentation during and after rifting. Unfortunately, however, many rifted margins are sediment‐starved, so the subsidence history is poorly known

Phosphate steering by Flap Endonuclease 1 promotes 5´-flap specificity and incision to prevent genome instability

DNA replication and repair enzyme Flap Endonuclease 1 (FEN1) is vital for genome integrity, and FEN1 mutations arise in multiple cancers. FEN1 precisely cleaves single-stranded (ss) 50-flaps one nucleotide into duplex (ds) DNA. Yet, how FEN1 selects for but does not incise the ss 50-flap was enigmatic. Here we combine crystallographic, biochemical and genetic analyses to show that two dsDNA binding sites set the 50polarity and to reveal unexpected control of the DNA phosphodiester backbone by electrostatic interactions. Via ‘phosphate steering’, basic residues energetically steer an inverted ss 50-flap through a gateway over FEN1’s active site and shift dsDNA for catalysis. Mutations of these residues cause an 18,000-fold reduction in catalytic rate in vitro and large-scale trinucleotide (GAA)n repeat expansions in vivo, implying failed phosphate-steering promotes an unanticipated lagging-strand template-switch mechanism during replication. Thus, phosphate steering is an unappreciated FEN1 function that enforces 50-flap specificity and catalysis, preventing genomic instability

The Dynamic Insulin Sensitivity and Secretion Test (DISST) - a novel measure of insulin sensitivity

Objective: To validate the methodology for the Dynamic Insulin Sensitivity and Secretion Test (DISST) and to demonstrate its potential in clinical and research settings. Methods: 123 men and women had routine clinical and biochemical measurements, an oral glucose tolerance test and a DISST. For the DISST, participants were cannulated for blood sampling and bolus administration. Blood samples were drawn at t=0, 10, 15, 25 and 35 minutes for measurement of glucose, insulin and C-peptide. A 10g bolus of intravenous glucose at t=5 minutes and 1U of intravenous insulin immediately after the t=15 minute sample were given. Fifty participants also had a hyperinsulinaemic euglycaemic clamp. Relationships between DISST insulin sensitivity (SI) and the clamp, and both DISST SI and secretion and other metabolic variables were measured. Results: A Bland-Altman plot showed little bias in the comparison of DISST with the clamp; with DISST underestimating the glucose clamp by 0.1·10-2·mg·l·kg-1·min-1·pmol-1 (90%CI -0.2 to 0). The correlation between SI as measured by DISST and the clamp was 0.82, the c unit for the ROC analysis for the two tests was 0.96. Metabolic variables showed significant correlations with DISST IS, and the second phase of insulin release. DISST also appears able to distinguish different insulin secretion patterns in individuals with identical SI values. Conclusions: DISST is a simple, dynamic test that compares favourably with the clamp in assessing SI and allows simultaneous assessment of insulin secretion. DISST has the potential to provide even more information about the pathophysiology of diabetes than more complicated tests

Phosphate steering by Flap Endonuclease 1 promotes 5´-flap specificity and incision to prevent genome instability

DNA replication and repair enzyme Flap Endonuclease 1 (FEN1) is vital for genome integrity, and FEN1 mutations arise in multiple cancers. FEN1 precisely cleaves single-stranded (ss) 50-flaps one nucleotide into duplex (ds) DNA. Yet, how FEN1 selects for but does not incise the ss 50-flap was enigmatic. Here we combine crystallographic, biochemical and genetic analyses to show that two dsDNA binding sites set the 50polarity and to reveal unexpected control of the DNA phosphodiester backbone by electrostatic interactions. Via ‘phosphate steering’, basic residues energetically steer an inverted ss 50-flap through a gateway over FEN1’s active site and shift dsDNA for catalysis. Mutations of these residues cause an 18,000-fold reduction in catalytic rate in vitro and large-scale trinucleotide (GAA)n repeat expansions in vivo, implying failed phosphate-steering promotes an unanticipated lagging-strand template-switch mechanism during replication. Thus, phosphate steering is an unappreciated FEN1 function that enforces 50-flap specificity and catalysis, preventing genomic instability

Morphologies of AGN host galaxies using HST/ACS in the CDFS-GOODS field

Using HST/ACS images in four bands F435W, F606W, F775W and F850LP, we identify optical counterparts to the X-ray sources in the Chandra Deep Field South in the GOODS South field. A detailed study has been made of these sources to study their morphological types. We use methods like decomposition of galaxy luminosity profiles, color maps and visual inspection of 192 galaxies which are identified as possible optical counterparts of Chandra X-ray sources in the CDFS-GOODS field. We find that most moderate luminosity AGN hosts are bulge dominated in the redshift range (z \approx 0.4-1.3), but not merging/interacting galaxies. This implies probable fueling of the moderate luminosity AGN by mechanisms other than those merger driven.Comment: pdflatex, accepted in ApSS. revisions in tex

What do people do with porn? qualitative research into the consumption, use and experience of pornography and other sexually explicit media

This article reviews qualitative research into the consumption of pornography and other sexually explicit media emerging from a range of subject areas. Taking a critique of quantitative methods and a focus on measuring sexual effects and attitudes as a starting point, it considers the proposition that qualitative work is more suited to an examination of the complex social, cultural and political constructions of sexuality. Examining studies into the way men, women and young people see, experience, and use explicit media texts, the article identifies the key findings that have emerged. Qualitative work shows that sexuality explicit media texts are experienced and understood in a variety of ways and evoke strong and often contradictory reactions, not all of which are represented in public debates about pornography. These texts function in a range of different ways, depending on context; as a source of knowledge, a resource for intimate practices, a site for identity construction, and an occasion for performing gender and sexuality. The article reviews these studies and their findings, identifying what they suggest about directions for future research, both in terms of developing methodology and refining approaches to sexuality and media consumption.</p

Optical Sum Rule in Finite Bands

In a single finite electronic band the total optical spectral weight or optical sum carries information on the interactions involved between the charge carriers as well as on their band structure. It varies with temperature as well as with impurity scattering. The single band optical sum also bears some relationship to the charge carrier kinetic energy and, thus, can potentially provide useful information, particularly on its change as the charge carriers go from normal to superconducting state. Here we review the considerable advances that have recently been made in the context of high $T_c$ oxides, both theoretical and experimental.Comment: Review article accepted for publication in J. Low Temp. Phys. 29 pages, 33 figure

Magnetic Fields, Relativistic Particles, and Shock Waves in Cluster Outskirts

It is only now, with low-frequency radio telescopes, long exposures with high-resolution X-ray satellites and gamma-ray telescopes, that we are beginning to learn about the physics in the periphery of galaxy clusters. In the coming years, Sunyaev-Zeldovich telescopes are going to deliver further great insights into the plasma physics of these special regions in the Universe. The last years have already shown tremendous progress with detections of shocks, estimates of magnetic field strengths and constraints on the particle acceleration efficiency. X-ray observations have revealed shock fronts in cluster outskirts which have allowed inferences about the microphysical structure of shocks fronts in such extreme environments. The best indications for magnetic fields and relativistic particles in cluster outskirts come from observations of so-called radio relics, which are megaparsec-sized regions of radio emission from the edges of galaxy clusters. As these are difficult to detect due to their low surface brightness, only few of these objects are known. But they have provided unprecedented evidence for the acceleration of relativistic particles at shock fronts and the existence of muG strength fields as far out as the virial radius of clusters. In this review we summarise the observational and theoretical state of our knowledge of magnetic fields, relativistic particles and shocks in cluster outskirts.Comment: 34 pages, to be published in Space Science Review